Guangdong Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, PR China.
Biopharm Drug Dispos. 2012 Apr;33(3):123-34. doi: 10.1002/bdd.1775. Epub 2012 Mar 17.
Naringin, a major active flavonone glycoside from a traditional Chinese medicine Huajuhong, has been demonstrated to have activities such as peripheral antitussive, mucoregulator and anti-inflammatory. The purpose of this study was to elucidate the metabolism and mass balance of orally administered naringin in rats and dogs. After oral administration of naringin to rats and dogs at doses of 42 mg/kg and 12.4 mg/kg, respectively, metabolites in excreta were identified using a LC-Q-TOF system. The major metabolites including naringin, total naringenin (including free naringenin and its conjugates) and 4-hydroxyphenylpropionic acid in excreta were quantified by a LC-MS/MS system. Twenty-two metabolites were identified in dogs and 17 metabolites were detected in rats. The observed routes of naringin metabolism were hydroxylation, methylation, acetylation, hydrogenation, deglycosylation, dehydrogenation, glucuronidation, sulfation, glucosylation, ring-fission, oxidation, glycine conjugation and dehydroxylation. On the basis of these identified metabolites, a comprehensive metabolic pathway of naringin was proposed. About 21% of administered naringin was recovered in rat excreta in the form of naringin, total naringenin and 4-hydroxyphenylpropionic acid, and about 60% was recovered in dog excreta. The levels of 4-hydroxyphenylpropionic acid in excreta were higher than those of naringin and total naringenin, and the quantified metabolites were excreted more through feces, rather than urine. Most of these metabolites were excreted within 36 h post dose. The results of metabolism and excretion studies provide an explanation for future pharmacological and toxicological findings and are the groundwork for clinical studies.
柚皮苷是一种源自中药化橘红的主要活性黄酮糖苷，具有镇咳、黏膜修复和抗炎等作用。本研究旨在阐明柚皮苷在大鼠和犬体内的口服代谢和物质平衡。大鼠和犬分别以 42mg/kg 和 12.4mg/kg 的剂量口服给予柚皮苷后，采用 LC-Q-TOF 系统鉴定排泄物中的代谢物。采用 LC-MS/MS 系统定量测定排泄物中的主要代谢物，包括柚皮苷、总柚皮素（包括游离柚皮素及其缀合物）和 4-羟基苯丙酸。在犬体内鉴定出 22 种代谢物，在大鼠体内检测到 17 种代谢物。观察到的柚皮苷代谢途径包括羟化、甲基化、乙酰化、氢化、去糖基化、脱氢、葡萄糖醛酸化、硫酸化、葡萄糖苷化、环裂、氧化、甘氨酸缀合和去羟化。基于这些鉴定出的代谢物，提出了柚皮苷的综合代谢途径。大鼠排泄物中以柚皮苷、总柚皮素和 4-羟基苯丙酸形式回收的给药柚皮苷约为 21%，犬排泄物中回收的给药柚皮苷约为 60%。排泄物中 4-羟基苯丙酸的水平高于柚皮苷和总柚皮素，且定量代谢物主要通过粪便排泄，而非尿液。这些代谢物大部分在给药后 36 小时内排泄。代谢和排泄研究的结果为未来的药理学和毒理学发现提供了解释，并为临床研究奠定了基础。
